Insight into how cells withstand DNA attacks could boost cancer research and more

Every cell in the body has its own power source in the form of mitochondria, and those energy producers have their own DNA. When that mitochondrial DNA breaks down, cells deploy enzymes to make repairs that will keep the energy flowing. Scientists led by the University of Sheffield have identified one of the enzymes that’s crucial to repairing damaged mitochondrial DNA—a finding they believe will enhance the search for effective cancer drugs and treatments for other diseases.

The enzyme, TDP1, is already known for its ability to repair DNA in the cell nucleus. In a five-year project, the researchers found that the enzyme also repairs mitochondrial DNA (mtDNA), by unleashing a protein called TOP1. That protein unravels knots that can form in DNA strands, according to a press release. The research was published in the journal Science Advances.

Cancerous cells divide rapidly, so they rely on a strong energy source. Sherif El-Khamisy, chair of molecular medicine at the University of Sheffield, believes that this enhanced understanding of how TDP1 facilitates mtDNA repair could point to therapies that aim to disrupt that process. "If we can find a way to selectively damage the mitochondria in the cancer cells, by preventing or slowing its repair mechanism, this could be really promising," he said in the release.

On the flip side, finding ways to promote mtDNA repair could boost the search for treatments for neurological disorders. It could also enhance the field of organ transplants, because mtDNA helps facilitate tissue regeneration.

And in the U.K. in particular, there’s one more potential application for this new insight into mtDNA repair. Mitochondrial replacement therapies were recently approved in the U.K. and are often called “three-parent babies,” because mtDNA is taken from a female donor and implanted into an embryo to correct mitochondrial disorders. El-Khamisy suggests assessing the function of TDP1 in donors to assure such procedures will succeed.

"It is important that we know as much as possible about how to identify healthy and defective mitochondria, in order to help those people with debilitating mitochondrial disease," Allan Pacey, a fertility expert at the University of Sheffield's Department of Oncology and Metabolism, said in the release.